Off-the-Shelf Nipple Engineering Neonipple Formation via Implantation of Scaffolded Decellularized Ovine Xenograft

Background Nipple reconstruction is widely regarded as the final step in postmastectomy breast reconstruction. While grafts, local flaps, or combination approaches have been used in nipple reconstruction, none has been able to achieve reliable long-term projection preservation. In response, we have sought to bioengineer neonipples in situ via the implantation of processed, decellularized cartilage xenografts placed within 3-dimensional-printed polylactic acid (PLA) scaffolds. Materials and Methods External nipple scaffolds were designed in-house and 3-dimensional-printed with PLA filament. Decellularized ovine xenograft infill was prepared and processed by mincing or zesting. All nipple scaffolds were placed subcutaneously on the dorsa of Sprague-Dawley rats and explanted after 1, 3, and 6 months for analysis. Results Explanted nipple scaffolds demonstrated gross maintenance of scaffold shape, diameter, and projection with accompanying increases in tissue volume. Histologic analyses revealed preservation of native cartilage architecture after 6 months without evidence of degradation. Analysis of formed tissue within the scaffolds revealed a progressive invasion of fibrovascular tissue with identifiable vascular channels and adipose tissue after 6 months in vivo. Confined compression testing revealed equilibrium moduli of both minced and zested samples that were within the expected range of previously reported human nipple tissue, while these data revealed no differences in the mechanical properties of the neotissue between time points or processing techniques. Conclusions These preliminary data support potential use of decellularized allograft to foster healthy tissue ingrowth within a PLA scaffold, thereby offering a novel solution to current limitations in nipple reconstruction.